Vijay Shankar Sharma - Academia.edu (original) (raw)
Papers by Vijay Shankar Sharma
International Journal of Dynamics and Control, Apr 17, 2023
Cureus
Background: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common ... more Background: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common rheumatologic problem with a prevalence of 22%-39% in India. Knee OA (KOA) is a major cause of mobility impairment, particularly among females. Non-surgical treatment options for KOA include intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA). Most commercially available PRP preparation kits do not remove RBCs and WBCs which are detrimental to the healing effects. Wockhardt Regenerative Pvt. Ltd., Mumbai, India has developed a kit known as Ossinext™ which has an advantage over traditional PRP in that it eliminates RBCs and WBCs. This study was conducted to evaluate the effectiveness and safety of intra-articular injection of Wockhardt's Ossinext™ an autologous growth factor concentrate (AGFC) versus HA in KOA. Methods: Male and female patients in the age group between 30 and 75 years with confirmed KOA on radiological assessment with Grades I-III on the Kellgren-Lawrence Grading Scale and with visual analog scale (VAS) pain score of 4 or more (on the numeric rating scale) in spite of taking non-steroidal antiinflammatory drugs (NSAIDs) since past 2 weeks were considered for study participation. This was an openlabeled study and eligible patients were randomly allocated to AGFC or HA in a 1:1 fashion. Three intraarticular injections were given in the affected knee joint, i.e. at baseline, month 1, and month 2 visits. Patients were evaluated at regular intervals, i.e. at months 5, 8, and 11 for primary and secondary endpoints. The primary efficacy endpoint for this study was change from baseline in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores at month 11 whereas the secondary efficacy endpoints were change from baseline of VAS pain scale at months 1, 2, 5, 8, and 11 as well as change from baseline of WOMAC, KOOS (Knee and Osteoarthritis Outcome System), and IKDC (International Knee Documentation Committee) scale at month 5, 8, and 11. For analysis a mixed model for repeated measures was used.
International Journal of Biomathematics
This work investigates the bifurcation analysis in a discrete-time Leslie–Gower predator–prey mod... more This work investigates the bifurcation analysis in a discrete-time Leslie–Gower predator–prey model with constant yield predator harvesting. The stability analysis for the fixed points of the discretized model is shown briefly. In this study, the model undergoes codimension-1 bifurcation such as fold bifurcation (limit point), flip bifurcation (period-doubling) and Neimark–Sacker bifurcation at a positive fixed point. Further, the model exhibits codimension-2 bifurcations, including Bogdanov–Takens bifurcation and generalized flip bifurcation at the fixed point. For each bifurcation, by using the critical normal form coefficient method, various critical states are calculated. To validate our analytical findings, the bifurcation curves of fixed points are drawn by using MATCONTM. The system exhibits interesting rich dynamics including limit cycles and chaos. Moreover, it has been shown that the predator harvesting may control the chaos in the system.
Data Analytics and Management, 2021
Stroke, 2015
Background: Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascu... more Background: Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascular diseases, including atrial fibrillation (AF). Recent studies have incriminated BNP as a marker of cardioembolic stroke. We aimed at investigating association of plasma BNP levels in acute ischemic stroke subtypes and their outcome in Indian patients. Methods: We recruited 270 acute ischemic stroke patients within 48 hours of symptom onset and compared with 110 age and sex matched control subjects. This study was carried out at Yashoda Hospital, Hyderabad, India between April 2011 and March 2013. Serum BNP levels were estimated in stroke patients and control subjects. Good functional outcome at 3-months was defined as modified Rankin score (mRS) ≤2. Results: Elevated BNP levels was significantly more in patients with acute ischemic stroke patients 119 (44%) compared to controls 4 (3.6%) (p<0.0001). Among stroke subtypes, elevated BNP levels were observed in 75% of cardioembolic str...
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Electroporation of artificial lipid membranes was studied by applying a l o p , 300-600mV rectang... more Electroporation of artificial lipid membranes was studied by applying a l o p , 300-600mV rectangular voltage clamp pulse followed by a ramp of negative slope which decayed to zero in the subsequent 5OOps. After the electroporating pulse the membrane conductance begins to increase after a variable time delay (latency time) and shows two distinct phases, a first phase in which conductance increases very rapidly followed by a second slow phase. The interrelationships between breakdown voltage, latency time and the membrane conductance were investigated in 25 different bilayers.
The Annals of thoracic surgery, 1994
Algorithms for Intelligent Systems, 2020
Molecular Imaging, 2006
Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has... more Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has enabled novel applications in molecular imaging. Membrane permeant peptides based on the HIV-1 Tat basic domain sequence, GRKKRRQRRR, labeled with fluorophores and fluorescent proteins for optical imaging or with appropriate peptide-based motifs or macrocycles to chelate metals, such as technetium for nuclear scintigraphy and gadolinium for magnetic resonance imaging, have been synthesized. In addition, iron oxide complexes have been functionalized with the Tat basic domain peptides for magnetic resonance imaging applications. Herein we review current applications of permeation peptides in molecular imaging and factors influencing permeation peptide internalization. These diagnostic agents show concentrative cell accumulation and rapid kinetics and display cytosolic and focal nuclear accumulation in human cells. Combining methods, dual-labeled permeation peptides incorporating fluorescein maleimide and chelated technetium have allowed for both qualitative and quantitative analysis of cellular uptake. Imaging studies in mice following intravenous administration of prototypic diagnostic permeation peptides show rapid whole-body distribution allowing for various molecular imaging applications. Strategies to develop permeation peptides into molecular imaging probes have included incorporation of targeting motifs such as molecular beacons or protease cleavable domains that enable selective retention, activatable fluorescence, or targeted transduction. These novel permeation peptide conjugates maintain rapid translocation across cell membranes into intracellular compartments and have the potential for targeted in vivo applications in molecular imaging and combination therapy. Mol Imaging (2006) 5, 1-15.
Molecular Imaging, 2006
Bioluminescence, positron emission tomography (PET), and fluorescence modalities are currently av... more Bioluminescence, positron emission tomography (PET), and fluorescence modalities are currently available for noninvasive imaging in vivo, each with its own merits. To exploit the combined strengths of each and facilitate multimodality imaging, we engineered a dual-reporter construct in which firefly luciferase (FLuc) and a 12-amino acid nonstructural linker were fused in frame to the Nterminus of a mutant herpes simplex virus thymidine kinase (mNLS-SR39TK) kinetically enhanced for positron emission tomography (PET). Furthermore, a triple-reporter construct was developed in which monster green fluorescent protein (MGFP), a recently available enhanced fluorescent protein, was introduced into the fusion vector downstream of an internal ribosome entry site (IRES) to allow analysis by fluorescence microscopy or flow cytometry without compromising the specific activities of the upstream fusion components. FLuc bioluminescence was measured with a cooled charge-coupled device camera and mNLS-SR39TK activity by 9-[4-[ 18 F]fluoro-3-(hydroxymethyl) butyl guanine (18 F-FHBG) microPET or 3 H-penciclovir net accumulation. Importantly, HeLa cells transiently transfected with the FLuc-mNLS-SR39TK-IRES-MGFP triple reporter retained the same specific activities of the FLuc-mNLS-SR39TK heteroenzyme and the individual unfused enzymes with no change in protein half-lives. The presence of the IRES-MGFP modestly decreased upstream heteroprotein expression. In living mice, somatic gene transfer of a ubiquitin promoter-driven FLuc-mNLS-SR39TK-IRES-MGFP plasmid showed a. 1,000-fold increase in liver photon flux and a. 2-fold increase in liver retention of 18 F-FHBG by microPET compared with mice treated with control plasmid. Multifocal hepatocellular fluorescence was readily observed by standard confocal microscopy. This second-generation triple reporter incorporating enhanced components enables bioluminescence, PET, and fluorescence imaging of cells and living animals.
Medicinal Chemistry, 2010
International Encyclopedia of Public Health, 2017
Common carotid occlusion in the rat significantly decreases the density of ,-adrenergic receptors... more Common carotid occlusion in the rat significantly decreases the density of ,-adrenergic receptors in preparations of microvessels obtained from ipsilateral and contralateral cerebral cortices. The disruption of nerve pathways connecting the hemispheres (callosal transection) partially reverses the effect of common carotid occlusion on /3-adrenergic receptor density in capillaries of the contralateral cortex. In addition, the destruction of the central noradrenergic system by intraventricular injection of 6-hydroxydopamine abolishes the effect of ischemia on capillary ,3-adrenergic receptor function in both hemispheres. The results suggest that /3-adrenergic receptors located on microvessels are partially regulated by neuronal pathways and that focal ischemia induces neurochemical and functional changes in remote areas of the brain. Circulation 73, No. 4, 784-788, 1986. THE BRAIN is extremely sensitive to ischemia; in fact the deprivation of blood supply induces a failure in synaptic transmission and neuronal death. Both neurotransmitter function and metabolism appear altered in various cerebral areas after ischemia.1-)2 These events are accompanied by changes in microvascular functions such as increased permeability to water and decreased glucose uptake and oxygen consumption. 3-16 Recent publications have demonstrated the existence of f3-adrenergic receptors coupled to adenylate cyclase in cerebral capillaries, which seem to be involved in the regulation of microvascular function. 17-24 In a previous study we investigated the effect of common carotid occlusion on f3-adrenergic receptor function in preparations of cerebral capillaries obtained from gerbils and rats.25' 26 The results indicated a significant decrease in the number of 8-adrenergic receptors in brain microvessels of both the ipsilateral and contralateral hemispheres. Notably, in occlusion of either the right or left carotid artery the reduction in receptor density is more pronounced in the left hemisphere,
Springer eBooks, 2002
The adaptive significance of circadian rhythms has been much speculated about but has not been su... more The adaptive significance of circadian rhythms has been much speculated about but has not been subjected to systematic and rigorous empirical investigation. The majority of the few empirical studies of the possible adaptive significance of circadian organisation suffer from numerous shortcomings that we can now identify based on hindsight gained through three decades of experimental work in evolutionary genetics. We present here some of the major findings from this work in evolutionary genetics that are relevant to the proper design and interpretation of experiments aiming at studying the adaptive significance of circadian organisation. We critically review past work on the adaptive significance of circadian organisation, and suggest that a long-term research programme combining selection studies on replicated sets of laboratory populations with a careful study of fitness effects of different light regimes on such populations is likely to prove far more fruitful than some of the approaches previously followed.
Journal of the Geological Society of India, 1990
Occurrences of radiolaria in the surface sediments collected at 22 stations in the Indian Ocean a... more Occurrences of radiolaria in the surface sediments collected at 22 stations in the Indian Ocean are noted. While some samples contain abundant radiolaria, others show extremely poor concentration, or, are practically devoid of them. A distinct relationship is found between radiolarian abundance and deep water current systems. It is suggested that the occurrence of radiolaria is largely controlled by currents which are responsible for dissolving radiolarian skeletons. The assemblage is dominated by warm-water species and also contains a few cold-water forms. The cold-water species are believed to be transported by the Antarctic Bottom Waters (AABW) to the present area.
The Journal of Experimental Zoology, 1998
The locomotor activity of the field mouse Mus booduga was monitored under continuous darkness (DD... more The locomotor activity of the field mouse Mus booduga was monitored under continuous darkness (DD) for extended periods of 275 to 388 days. Free-running period (tau), activity time (alpha) and rest time (rho) were computed from the activity records for all the animals (n = 10). Decreases in the circadian period (tau) with age were observed in some of the animals at an early age (< ca. 100 days) and then tau remained relatively constant for rest of their life span. The activity time (alpha), rest time (rho), and their ratio (alpha/rho), however, did not show any consistent trend of increase/decrease. The initial decrease in tau is consistent with previous models suggesting a time-dependent increase in the number of cells generating oscillations in the suprachiasmatic nucleus (SCN) and/or increase in the strength of coupling between these cells. In such models, after an optimal number of cells launch themselves into a state of self-sustained oscillation, tau stabilizes, achieving relative constancy, a pattern similar to the one observed in our study.
International Journal of Dynamics and Control, Apr 17, 2023
Cureus
Background: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common ... more Background: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common rheumatologic problem with a prevalence of 22%-39% in India. Knee OA (KOA) is a major cause of mobility impairment, particularly among females. Non-surgical treatment options for KOA include intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA). Most commercially available PRP preparation kits do not remove RBCs and WBCs which are detrimental to the healing effects. Wockhardt Regenerative Pvt. Ltd., Mumbai, India has developed a kit known as Ossinext™ which has an advantage over traditional PRP in that it eliminates RBCs and WBCs. This study was conducted to evaluate the effectiveness and safety of intra-articular injection of Wockhardt's Ossinext™ an autologous growth factor concentrate (AGFC) versus HA in KOA. Methods: Male and female patients in the age group between 30 and 75 years with confirmed KOA on radiological assessment with Grades I-III on the Kellgren-Lawrence Grading Scale and with visual analog scale (VAS) pain score of 4 or more (on the numeric rating scale) in spite of taking non-steroidal antiinflammatory drugs (NSAIDs) since past 2 weeks were considered for study participation. This was an openlabeled study and eligible patients were randomly allocated to AGFC or HA in a 1:1 fashion. Three intraarticular injections were given in the affected knee joint, i.e. at baseline, month 1, and month 2 visits. Patients were evaluated at regular intervals, i.e. at months 5, 8, and 11 for primary and secondary endpoints. The primary efficacy endpoint for this study was change from baseline in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores at month 11 whereas the secondary efficacy endpoints were change from baseline of VAS pain scale at months 1, 2, 5, 8, and 11 as well as change from baseline of WOMAC, KOOS (Knee and Osteoarthritis Outcome System), and IKDC (International Knee Documentation Committee) scale at month 5, 8, and 11. For analysis a mixed model for repeated measures was used.
International Journal of Biomathematics
This work investigates the bifurcation analysis in a discrete-time Leslie–Gower predator–prey mod... more This work investigates the bifurcation analysis in a discrete-time Leslie–Gower predator–prey model with constant yield predator harvesting. The stability analysis for the fixed points of the discretized model is shown briefly. In this study, the model undergoes codimension-1 bifurcation such as fold bifurcation (limit point), flip bifurcation (period-doubling) and Neimark–Sacker bifurcation at a positive fixed point. Further, the model exhibits codimension-2 bifurcations, including Bogdanov–Takens bifurcation and generalized flip bifurcation at the fixed point. For each bifurcation, by using the critical normal form coefficient method, various critical states are calculated. To validate our analytical findings, the bifurcation curves of fixed points are drawn by using MATCONTM. The system exhibits interesting rich dynamics including limit cycles and chaos. Moreover, it has been shown that the predator harvesting may control the chaos in the system.
Data Analytics and Management, 2021
Stroke, 2015
Background: Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascu... more Background: Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascular diseases, including atrial fibrillation (AF). Recent studies have incriminated BNP as a marker of cardioembolic stroke. We aimed at investigating association of plasma BNP levels in acute ischemic stroke subtypes and their outcome in Indian patients. Methods: We recruited 270 acute ischemic stroke patients within 48 hours of symptom onset and compared with 110 age and sex matched control subjects. This study was carried out at Yashoda Hospital, Hyderabad, India between April 2011 and March 2013. Serum BNP levels were estimated in stroke patients and control subjects. Good functional outcome at 3-months was defined as modified Rankin score (mRS) ≤2. Results: Elevated BNP levels was significantly more in patients with acute ischemic stroke patients 119 (44%) compared to controls 4 (3.6%) (p<0.0001). Among stroke subtypes, elevated BNP levels were observed in 75% of cardioembolic str...
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Electroporation of artificial lipid membranes was studied by applying a l o p , 300-600mV rectang... more Electroporation of artificial lipid membranes was studied by applying a l o p , 300-600mV rectangular voltage clamp pulse followed by a ramp of negative slope which decayed to zero in the subsequent 5OOps. After the electroporating pulse the membrane conductance begins to increase after a variable time delay (latency time) and shows two distinct phases, a first phase in which conductance increases very rapidly followed by a second slow phase. The interrelationships between breakdown voltage, latency time and the membrane conductance were investigated in 25 different bilayers.
The Annals of thoracic surgery, 1994
Algorithms for Intelligent Systems, 2020
Molecular Imaging, 2006
Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has... more Rapid and efficient delivery of imaging probes to the cell interior using permeation peptides has enabled novel applications in molecular imaging. Membrane permeant peptides based on the HIV-1 Tat basic domain sequence, GRKKRRQRRR, labeled with fluorophores and fluorescent proteins for optical imaging or with appropriate peptide-based motifs or macrocycles to chelate metals, such as technetium for nuclear scintigraphy and gadolinium for magnetic resonance imaging, have been synthesized. In addition, iron oxide complexes have been functionalized with the Tat basic domain peptides for magnetic resonance imaging applications. Herein we review current applications of permeation peptides in molecular imaging and factors influencing permeation peptide internalization. These diagnostic agents show concentrative cell accumulation and rapid kinetics and display cytosolic and focal nuclear accumulation in human cells. Combining methods, dual-labeled permeation peptides incorporating fluorescein maleimide and chelated technetium have allowed for both qualitative and quantitative analysis of cellular uptake. Imaging studies in mice following intravenous administration of prototypic diagnostic permeation peptides show rapid whole-body distribution allowing for various molecular imaging applications. Strategies to develop permeation peptides into molecular imaging probes have included incorporation of targeting motifs such as molecular beacons or protease cleavable domains that enable selective retention, activatable fluorescence, or targeted transduction. These novel permeation peptide conjugates maintain rapid translocation across cell membranes into intracellular compartments and have the potential for targeted in vivo applications in molecular imaging and combination therapy. Mol Imaging (2006) 5, 1-15.
Molecular Imaging, 2006
Bioluminescence, positron emission tomography (PET), and fluorescence modalities are currently av... more Bioluminescence, positron emission tomography (PET), and fluorescence modalities are currently available for noninvasive imaging in vivo, each with its own merits. To exploit the combined strengths of each and facilitate multimodality imaging, we engineered a dual-reporter construct in which firefly luciferase (FLuc) and a 12-amino acid nonstructural linker were fused in frame to the Nterminus of a mutant herpes simplex virus thymidine kinase (mNLS-SR39TK) kinetically enhanced for positron emission tomography (PET). Furthermore, a triple-reporter construct was developed in which monster green fluorescent protein (MGFP), a recently available enhanced fluorescent protein, was introduced into the fusion vector downstream of an internal ribosome entry site (IRES) to allow analysis by fluorescence microscopy or flow cytometry without compromising the specific activities of the upstream fusion components. FLuc bioluminescence was measured with a cooled charge-coupled device camera and mNLS-SR39TK activity by 9-[4-[ 18 F]fluoro-3-(hydroxymethyl) butyl guanine (18 F-FHBG) microPET or 3 H-penciclovir net accumulation. Importantly, HeLa cells transiently transfected with the FLuc-mNLS-SR39TK-IRES-MGFP triple reporter retained the same specific activities of the FLuc-mNLS-SR39TK heteroenzyme and the individual unfused enzymes with no change in protein half-lives. The presence of the IRES-MGFP modestly decreased upstream heteroprotein expression. In living mice, somatic gene transfer of a ubiquitin promoter-driven FLuc-mNLS-SR39TK-IRES-MGFP plasmid showed a. 1,000-fold increase in liver photon flux and a. 2-fold increase in liver retention of 18 F-FHBG by microPET compared with mice treated with control plasmid. Multifocal hepatocellular fluorescence was readily observed by standard confocal microscopy. This second-generation triple reporter incorporating enhanced components enables bioluminescence, PET, and fluorescence imaging of cells and living animals.
Medicinal Chemistry, 2010
International Encyclopedia of Public Health, 2017
Common carotid occlusion in the rat significantly decreases the density of ,-adrenergic receptors... more Common carotid occlusion in the rat significantly decreases the density of ,-adrenergic receptors in preparations of microvessels obtained from ipsilateral and contralateral cerebral cortices. The disruption of nerve pathways connecting the hemispheres (callosal transection) partially reverses the effect of common carotid occlusion on /3-adrenergic receptor density in capillaries of the contralateral cortex. In addition, the destruction of the central noradrenergic system by intraventricular injection of 6-hydroxydopamine abolishes the effect of ischemia on capillary ,3-adrenergic receptor function in both hemispheres. The results suggest that /3-adrenergic receptors located on microvessels are partially regulated by neuronal pathways and that focal ischemia induces neurochemical and functional changes in remote areas of the brain. Circulation 73, No. 4, 784-788, 1986. THE BRAIN is extremely sensitive to ischemia; in fact the deprivation of blood supply induces a failure in synaptic transmission and neuronal death. Both neurotransmitter function and metabolism appear altered in various cerebral areas after ischemia.1-)2 These events are accompanied by changes in microvascular functions such as increased permeability to water and decreased glucose uptake and oxygen consumption. 3-16 Recent publications have demonstrated the existence of f3-adrenergic receptors coupled to adenylate cyclase in cerebral capillaries, which seem to be involved in the regulation of microvascular function. 17-24 In a previous study we investigated the effect of common carotid occlusion on f3-adrenergic receptor function in preparations of cerebral capillaries obtained from gerbils and rats.25' 26 The results indicated a significant decrease in the number of 8-adrenergic receptors in brain microvessels of both the ipsilateral and contralateral hemispheres. Notably, in occlusion of either the right or left carotid artery the reduction in receptor density is more pronounced in the left hemisphere,
Springer eBooks, 2002
The adaptive significance of circadian rhythms has been much speculated about but has not been su... more The adaptive significance of circadian rhythms has been much speculated about but has not been subjected to systematic and rigorous empirical investigation. The majority of the few empirical studies of the possible adaptive significance of circadian organisation suffer from numerous shortcomings that we can now identify based on hindsight gained through three decades of experimental work in evolutionary genetics. We present here some of the major findings from this work in evolutionary genetics that are relevant to the proper design and interpretation of experiments aiming at studying the adaptive significance of circadian organisation. We critically review past work on the adaptive significance of circadian organisation, and suggest that a long-term research programme combining selection studies on replicated sets of laboratory populations with a careful study of fitness effects of different light regimes on such populations is likely to prove far more fruitful than some of the approaches previously followed.
Journal of the Geological Society of India, 1990
Occurrences of radiolaria in the surface sediments collected at 22 stations in the Indian Ocean a... more Occurrences of radiolaria in the surface sediments collected at 22 stations in the Indian Ocean are noted. While some samples contain abundant radiolaria, others show extremely poor concentration, or, are practically devoid of them. A distinct relationship is found between radiolarian abundance and deep water current systems. It is suggested that the occurrence of radiolaria is largely controlled by currents which are responsible for dissolving radiolarian skeletons. The assemblage is dominated by warm-water species and also contains a few cold-water forms. The cold-water species are believed to be transported by the Antarctic Bottom Waters (AABW) to the present area.
The Journal of Experimental Zoology, 1998
The locomotor activity of the field mouse Mus booduga was monitored under continuous darkness (DD... more The locomotor activity of the field mouse Mus booduga was monitored under continuous darkness (DD) for extended periods of 275 to 388 days. Free-running period (tau), activity time (alpha) and rest time (rho) were computed from the activity records for all the animals (n = 10). Decreases in the circadian period (tau) with age were observed in some of the animals at an early age (< ca. 100 days) and then tau remained relatively constant for rest of their life span. The activity time (alpha), rest time (rho), and their ratio (alpha/rho), however, did not show any consistent trend of increase/decrease. The initial decrease in tau is consistent with previous models suggesting a time-dependent increase in the number of cells generating oscillations in the suprachiasmatic nucleus (SCN) and/or increase in the strength of coupling between these cells. In such models, after an optimal number of cells launch themselves into a state of self-sustained oscillation, tau stabilizes, achieving relative constancy, a pattern similar to the one observed in our study.